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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA division of Rheumatology and clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

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World Journal of Gastroenterology 2024年第10期30卷 1368-1376页

作者： Nobukazu Agatsuma Takahiro Utsumi Yoshitaka Nishikawa Takahiro Horimatsu Takeshi Seta Yukitaka Yamashita Yukari Tanaka Takahiro Inoue Yuki Nakanishi Takahiro Shimizu Mikako Ohno Akane Fukushima Takeo Nakayama Hiroshi Seno Department of Gastroenterology and Hepatology Kyoto University Graduate School of MedicineKyoto 606-8507Japan Department of Gastroenterology and Hepatology Japanese Red Cross Wakayama Medical CenterWakayama 640-8558Japan Department of Health Informatics Kyoto University School of Public HealthKyoto 606-8501Japan Institute for Advancement of clinical and Translational Science(iACT) Kyoto University HospitalKyoto 606-8507Japan Medical Support Section Medical Affairs DivisionKyoto University HospitalKyoto 606-8507Japan

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor *** efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside *** identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less *** the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related *** To clarify the stage at CRC diagnosis based on diagnostic *** We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two *** diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and *** early-stage was defined as Stages 0 or *** and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up *** adjusted covariates were age,sex,and tumor *** Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,*** the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,*** symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening gro

关键词： Colorectal neoplasms Cancer registry Diagnostic route Cancer screening Stage at diagnosis

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Echocardiographic predictors and associated outcomes of multiple vegetations in infective endocarditis:A pilot study

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World Journal of Cardiology 2024年第6期16卷 318-328页

作者： Ajay Kumar Mishra Kannu Bansal Ibragim Al-Seykal Pradnya B Bhattad Anu Anna George Anil Jha Nitish Sharma Jennifer Sargent Mark J Kranis division of Cardiology Saint Vincent HospitalWorcesterMA 01608United States Department of Internal Medicine Saint Vincent HospitalWorcesterMA 01608United States Department of Medicine Division of CardiologySaint Vincent HospitalWorcesterMA 01608United States division of Cardiovascular Medicine Saint Vincent HospitalWorcesterMA 01608United States

BACKGROUND Infective endocarditis(IE)is a life-threatening infection with an annual mortality of 40%.Embolic events reported in up to 80%of *** of>10 mm size are associated with increased embolic events and poor *** is a paucity of literature on the association of multiple vegetations with *** To study the echocardiographic(ECHO)features and outcomes associated with the presence of multiple *** In this retrospective,single-center,cohort study patients diagnosed with IE were recruited from June 2017 to June 2019.A total of 84 patients were diagnosed to have IE,of whom 67 with vegetation were *** demographic,clinical,laboratory,and ECHO parameters were *** that were studied included recurrent admission,embolic phenomenon,and *** Twenty-three(34%)patients were noted to have multiple vegetations,13(56.5%)were male and 10(43.5%)were *** mean age of these patients was ***(35%)had a prior episode of *** features of moderate to severe valvular regurgitation[odds ratio(OR)=4],presence of pacemaker lead(OR=4.8),impaired left ventricle(LV)relaxation(OR=4),and elevated pulmonary artery systolic pressure(PASP)(OR=2.2)are associated with higher odds of multiple *** these moderate to severe valvular regurgitation(P=0.028),pacemaker lead(P=0.039)and impaired relaxation(P=0.028)were statistically *** patients were noted to have an increased association of recurrent admissions(OR=3.6),recurrent bacteremia(OR=2.4),embolic phenomenon(OR=2.5),intensive care unit stay(OR=2.8),hypotension(OR=2.1),surgical intervention(OR=2.8)and device removal(OR=4.8).Of this device removal(P=0.039)and recurrent admissions(P=0.017)were statistically *** This study highlights the associations of ECHO predictors and outcomes in patients with IE having multiple *** features of moderate to severe regurgitation,presence of pacemaker lead,impai

关键词： Endocarditis Echocardiography Vegetations Predictors Outcome

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Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar Department of Basic Pharmaceutical Sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey Health Sciences Faculty Recep Tayyip Erdogan UniversityRize 53350Turkey Molecular Oncology division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey Molecular Medicine division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of clinical Cases 2023 November 6;11(31):*** all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural *** methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized *** is a popular technique for collecting direct mea-surements of metabolic activity from many biological ***,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme *** annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called *** network uses an approach that emphasizes metabolite-gene consensus via biochemical *** metabolomics and genomics data is ***,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical *** The genome and metabolites of biological organisms are not fully characterized with current ***,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug *** network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical ***,clinical data may be integrated to gene expression–metabolite expression by system genetics appr

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer

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Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus

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CCS Chemistry 2024年第2期6卷 487-496页

作者： Ke Sun Zhe Ding Xiaoying Jia Haonan Cheng Yingwen Li Yan Wu Zhuoyu Li Xiaohua Huang Fangxu Pu Entao Li Guiyou Wang Wei Wang Yun Ding Gary Wong Sandra Chiu Jiaming Lan Aiguo Hu Shanghai Key Laboratory of Advanced Polymeric Materials School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237 CAS Key Laboratory of Molecular Virology&Immunology Chinese Academy of SciencesShanghai 200031 University of the Chinese Academy of Sciences Beijing 100049 State Key Laboratory of Virology Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071 division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230027 Department of clinical Laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has claimedmillions of lives and caused innumerable economic losses ***,state-of-the-art treatments still lag behind the continual emergence of new *** to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural ***,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)*** core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus,while the hyperanion groups ensure negligible cytotoxicity of the *** EDYs exhibit antiviral activity down to nanomolar concentrations,and the selectivity index of up to 20,000 against four kinds of human coronavirus,including the SARS-CoV-2 Omicron variant,suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future“disease X.”

关键词： enediyne broad spectrum antiviral protein disintegration coronavirus polyanions

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A novel homozygous missense variant in ARSK causes MPS X,a new subtype of mucopolysaccharidosis

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Genes & Diseases 2024年第3期11卷 87-90页

作者： Miao Sun Cornelia K.Kaminsky Philip Deppe Mai-Brittllse Frederic M.Vaz Barbara Plecko Torben Lubke Linda M.Randolph division of Genomic Medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany Amsterdam UMC Location University of Amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands Amsterdam Gastroenterology Endocrinology Metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core Facility Metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands Department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria division of Medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

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RNF6 promotes chronic myelogenous leukemia cell proliferation and migration by stabilizing vimentin via multiple atypical ubiquitinations

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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of clinical Pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China division of Hematology&Oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene *** addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia

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Advancements in hemostatic strategies for managing upper gastrointestinal bleeding: A comprehensive review

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World Journal of Gastroenterology 2024年第15期30卷 2087-2090页

作者： Ah Young Lee Joo Young Cho division of Gastroenterology Department of Internal MedicineCha Gangnam Medical CenterCha University College of MedicineSeoul 06135Korea

Upper gastrointestinal(GI)hemorrhage presents a substantial clinical *** management typically involves resuscitation and endoscopy within 24 h,although the benefit of very early endoscopy(<12 h)for high-risk patients is *** goals include stopping acute bleeding,preventing rebleeding,and using a multimodal approach encompassing endoscopic,pharmacological,angiographic,and surgical *** agents such as vasopressin,prostaglandins,and proton pump inhibitors are effective,but the increase in antithrombotic use has increased GI bleeding *** hemostasis,particularly for nonvariceal bleeding,employs techniques such as electrocoagu-lation and heater probes,with concerns over tissue injury from monopolar *** methods such as Hemospray and Endoclot show promise in creating mechanical tamponades but have ***,the first-line therapy includes thermal probes and hemoclips,with over-the-scope clips emerging for larger ulcer *** gold probe,combining bipolar electrocoagulation and injection,offers targeted coagulation but has faced device-related *** advancements involve combining techniques and improving endoscopic imaging,with studies exploring combined approaches showing *** research is crucial for developing standardized and effective hemorrhage management strategies.

关键词： Upper gastrointestinal bleeding Hemostasis Endoscopy Probe Spray Clip

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2024 Adult Compendium of Physical Activities:A third update of the energy costs of human activities

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Journal of Sport and Health Science 2024年第1期13卷 6-12页

作者： Stephen D.Herrmann Erik A.Willis Barbara E.Ainsworth Tiago V.Barreira Mary Hastert Chelsea L.Kracht John M.Schuna Jr. Zhenghui Cai Minghui Quan Catrine Tudor-Locke Melicia C.Whitt-Glover David R. Jacobs Jr. Kansas Center for Metabolism and Obesity Research University of Kansas Medical CenterKansas CityKS 66160USA division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA Center for Health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA School of Exercise and Health Shanghai University of SportShanghai 200438China Exercise Science Department Syracuse UniversitySyracuseNY 13244USA clinical Sciences division Pennington Biomedical Research CenterBaton RougeLA 70808USA School of Exercise and Sport Science Oregon State UniversityCorvallisOR 97331USA College of Health and Human Services University of North Carolina at CharlotteCharlotteNC 28223USA Gramercy Research Group KnightdaleNC 27545USA division of Epidemiology and Community Health School of Public HealthUniversity of MinnesotaMinneapolisMN 55454USA

Background:The Compendium of Physical Activities was published in 1993 to improve the comparability of energy expenditure values assigned to self-reported physical activity(PA)across *** original version was updated in 2000,and again in 2011,and has been widely used to support PA research,practice,and public health ***:This 2024 update was tailored for adults 19-59 years of age by removing data from those≥60 *** a systematic review and supplementary searches,we identified new activities and their associated measured metabolic equivalent(MET)values(using indirect calorimetry)published since *** replaced estimated METs with measured values when ***:We screened 32,173 abstracts and 1507 full-text papers and extracted 2356 PA energy expenditure values from 701 *** added303 new PAs and adjusted 176 existing MET values and descriptions to reflect the addition of new data and removal of METs for older *** added a Major Heading(Video Games).The 2024 Adult Compendium includes 1114 PAs(912 with measured and 202 with estimated values)across 22 Major ***:This comprehensive update and refinement led to the creation of The 2024 Adult Compendium,which has utility across research,public health,education,and healthcare domains,as well as in the development of consumer health *** new website with the complete lists of PAs and supporting resources is available at https://***.

关键词： Adults Energy expenditure Exercise MET Physical Activities

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Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement

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International Journal of Oral Science 2024年第2期16卷 238-250页

作者： Liyuan Chen Huajie Yu Zixin Li Yu Wang Shanshan Jin Min Yu Lisha Zhu Chengye Ding Xiaolan Wu Tianhao Wu Chunlei Xun Yanheng Zhou Danqing He Yan Liu Department of Orthodontics Central LaboratoryPeking University School and Hospital for Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Peking University Hospital of Stomatology Fourth division BeijingChina

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory *** tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor ***,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains *** this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling *** or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling *** Caspase-1^(−/−)mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on ***,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced ***,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor ***,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

关键词： homeostasis movement thereby

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